Browsing by Author "Shamley, Delva"
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- ItemOpen AccessAxillary web syndrome after treatment for breast cancer: An exploration of imaging evidence of fascial changes and its relationship to clinical variables(2019) Paulssen, Kyle Joseph Catharina; Shamley, Delva; Slater, CharlesBreast cancer is the most commonly diagnosed cancer in women and surgery remains the primary treatment. Evaluation of tumour spread is done by axillary lymph node assessment by surgical excision. Such invasive treatments, in conjunction with adjuvant therapies such as chemotherapy, radiotherapy and hormonal therapy, may alter patient healing patterns giving rise to complications such as axillary web syndrome (AWS). AWS presents as a puckering web of axillary skin overlying a cord of tissue that tightens with shoulder abduction. It is painful, limits shoulder range of movement (ROM) and reduces the quality of life of the patients. The syndrome is elusive, does not occur in everyone and is thought to be self-limiting in nature with spontaneous cord resolution. Evidence, however, is pointing towards long-term morbidity in some patients. The cord itself has been hypothesised to be lymphatic or vascular in origin and damage during axillary surgery gives rise to the structure. Anatomically, the vascular structures are bound by the connective tissue network of fascia. The adhesive and puckering appearance of the cord on clinical examination and in limited biopsy studies could imply a possible role of damaged fascia in the syndrome. The fascia, as a three-dimensional body-wide network, has been shown to be a functional unit with the musculoskeletal system and is important in coordinating movement. Furthermore, the fascia contains numerous receptors imperative for proprioceptive and nociceptive functioning. The fibroblast cells and fibres that it comprises are involved in tissue healing and scar tissue formation. Chronic inflammation upon fascial damage can lead to tissue adhesions and fibrosis, rendering a non-functional scar. Ultrasonography (US) has been able to visualise fascial differences and has been used to examine fascial abnormalities including scars and adhesions. Physiotherapy treatment has been shown to aid in remobilising scar tissue and in being able to help improve morbidity in AWS patients. The authors therefore hypothesised that damaged fascia contributes to the symptomology of AWS. The present study set out to evaluate whether altered fascia plays a role in the syndrome using fascial explanations for risk factors in the AWS literature and US in patients with AWS to observe anatomical changes. Furthermore, the authors hypothesised that myofascial physiotherapy could aid in cord resolution and symptom improvement and that it would reflect in fascial changes on US. The current descriptive, observational, pilot, proof-of-concept case-series study focused on fascial changes before and after myofascial release physiotherapy in women presenting with AWS following breast cancer treatment (n = 11). At the time points, US in the area of interest (the axilla) and MRI scans of a single patient were done pre-physiotherapy. Furthermore, patient variables of ROM, pain and disability using the SPADI questionnaire, and quality of life using the FACT-B questionnaire, were evaluated to relate to any fascial differences between affected and unaffected arms on US and compared to findings after physiotherapy to determine trends. To observe fascial continuity, alignment of US scans was attempted. The results from the case studies and overall trends indicated thickened fascia, reduced continuity, decreased gliding potential and increased adherence between the different fascial layers on US in the majority of patients on the affected arm in the area of interest suggesting that they are changes resulting from the treatment. The findings related to the external cord appearance. On MRI, a fibrous band of tissue was observed connecting to muscles and skin. The findings were found to descriptively show a trend with reduced ROM and increased SPADI scores. No descriptive relationship with FACT-B was noted. Several patients (n = 6) continued with physiotherapy for six treatments. The treatment proved beneficial for all patients, who improved on ROM and SPADI scores. However, not all their symptoms were completely resolved. The findings corroborate observations on US showing improved gliding, more regular and organised fascia, and less adhesions post-physiotherapy. Cord resolution or reduction occurred in half of the patients. Risk factors for AWS as identified in the literature and related to the patients, such as more invasive treatments and (neo)adjuvant therapies, were explained to cause more fibrosis and possibly contributed to the symptoms seen but could not be verified in the study due to the small, varied sample. Furthermore, due to the difficulty of finding suitable patients and the low sample size, the current study could not statistically corroborate many correlations and hence was limited to descriptive trend description. Using the fascial literature, restricted fascia and adhesions could be explained to lead to biomechanical limitations, explaining reduced ROM and nociceptor activation as seen in pain reported in the study. A fibrosed vessel damaged during axillary surgery as well as surrounding fascial changes, which occurred as the result of the healing response, could explain the varying appearances of the cord. The author concluded that the trends seen suggest a link for morbidity resulting from fascial damage and adds weight to the evidence of fascial involvement in AWS. Wider fascial involvement on US and MRI descriptively related to the presence of cording, limited shoulder ROM and pain before and improvements and changes in the domains after physiotherapy, supported the hypotheses. The present study highlighted that myofascial release can be beneficial for patients suffering from AWS and suggests that US may be a feasible outcome measure to aid in evaluating fascia and fibrosis subsequent to physiotherapy, guide it and determine its efficacy. Furthermore, risk factors need to be identified to implement an early warning system for the sequelae of breast cancer so that patients at risk are identified timeously and receive the help they need to minimise the effect of the syndrome on their wellbeing in order to improve their quality of life.
- ItemOpen AccessOlder Adults’ Experience of an Exergaming Intervention to Improve Balance and Prevent Falls: A Nested Explanatory Qualitative Study(2021-12-09) Rogers, Christine; Shamley, Delva; Amosun, SeyiFalls are frequent and life-changing events for older adults worldwide. The ageing phenomenon has arrived in developing countries, which experience tensions between curative and rehabilitative services, combined with an increase in non-communicable diseases. Policies addressing issues of ageing have been poorly implemented, and there are few fall prevention initiatives. Compelling evidence from the Global North supports exercise-based interventions to improve balance and reduce fall risk in older adults. More recently, attention has focused on interactive videogaming, known as exergames, as a novel way to manage fall risk with exercise. Commercially available exergames have inherent appeal for low- and middle-income country contexts, where rehabilitation professionals and resources are scanty. The aim of this study was to explore the feasibility of a large-scale randomized control trial comparing an exergaming intervention with the gold-standard Otago Exercise Programme and a no-intervention arm. Exercise adherence was poor in both intervention arms, and this prompted a shift to mixed methodology to explore the construct of falls and participants’ experience of the exergaming intervention. Focus groups were conducted, and the results were analysed using content analysis. Whereas the results demonstrated improvements in physical outcome measures (e.g., Timed-Up-and-Go, MiniBESTest) related to balance and falls that were encouraging in both the gold-standard and exergaming intervention groups, few participants achieved optimal adherence. Attitudes toward falls and fall prevention were explored, as well as participants’ experiences of the exergaming programme. Consistent with a developing country context, participants acknowledged both intrinsic and extrinsic fall risk factors. Exergaming participants enjoyed the fun and playful aspects of the exercise programme, yet these were not sufficient to maximize adherence. The focus groups described the barriers and facilitators to participation, which included motivation. The focus groups discussed strategies to enhance participation, and these are discussed in the context of exergaming.
- ItemOpen AccessPrevalence of shoulder morbidity after treatment for breast cancer in South Africa(2018) Kramer, Nicole; Shamley, Delva; Ramjith, JordacheIntroduction: Breast cancer is the most frequently diagnosed cancer and leading cause of cancer death among women and represents a considerable public health burden in South Africa and other low-middle income countries. Breast cancer management comprises single or combination treatment including surgery, radiotherapy and chemotherapy. Short and long-term complications of these treatments include shoulder morbidities such as pain, decreased range of motion, tightness, weakness, pain, numbness and lymphoedema, and may be present for up to 6 years post-surgery. An understanding of baseline demographic and clinical risk factors can guide rehabilitation and management strategies for high risk patients. Materials and Methods: This study was a cross-sectional analysis of the prevalence of shoulder pain and dysfunction in women attending their post-treatment annual follow up visit for unilateral breast carcinoma. The aim of this study was to quantify the burden of shoulder pain and disability in a tertiary academic hospital in Cape Town, South Africa, and identify potential risk factors for the development of shoulder morbidity. The primary objective of this study was to determine the prevalence of shoulder morbidity and the secondary objective was to evaluate associations between shoulder morbidity and risk factors such as treatment protocol or baseline demographics. Results: The majority of patients were of mixed ancestry, had their left side affected, received ALND and had undergone Modified Radical Mastectomy. The mean age was 60 years with a mean follow-up since surgery of 6 years. Three-quarters of patients reported a presence of pain or disability; 9% experienced severe pain and disability. Multivariable ordinal logistic regression analysis identified race, side, axillary surgery, chemotherapy and age as significant predictors of pain, and chemotherapy a significant predictor of disability. Discussion: The substantial burden of shoulder morbidity in this population represents a significant public health burden. The use of identified clinical and demographic characteristics may guide in the development of survivorship programmes incorporating surveillance and management of these high risk patients.
- ItemOpen AccessA scoping review examining the integration of exercise services in clinical oncology settings(2022-02-21) Ezenwankwo, Elochukwu F; Nnate, Daniel A; Usoro, Godspower D; Onyeso, Chimdimma P; Anieto, Ijeoma B; Ibeneme, Sam C; Albertus, Yumna; Lambert, Victoria E; Ezeukwu, Antoninus O; Abaraogu, Ukachukwu O; Shamley, DelvaBackground Addressing questions surrounding the feasibility of embedding exercise service units in clinical oncology settings is imperative for developing a sustainable exercise-oncology clinical pathway. We examined available literature and offered practical recommendations to support evidence-based practice, policymaking, and further investigations. Methods Four thousand eight hundred sixty-three unique records identified in Embase, CINAHL, MEDLINE, Web of Science Core Collection, and ProQuest (Health and Medicine) were screened for studies that recruited cancer patients, assessed the co-location of exercise service and cancer treatment units, and reported findings on service implementation. Evidence from six studies providing data from over 30 programs was integrated using narrative synthesis. Results Service implementation was relatively modest across the included studies. Exercise services were delivered by physiotherapists, exercise physiologists, and kinesiologists and funded mainly through grants and private donations, with staff salaries accruing as the major expense. Service penetration, adoption, and acceptability were generally low. However, studies recorded high clinician/patient satisfaction. Major barriers to service integration were limited funding, lack of detailed implementation plan, and low organizational buy-in. Common reasons for non-utilization, missed sessions, and dropouts were lack of interest, unwellness, hospital readmission, disease progression, and adverse skeletal events. Conclusion Implementing exercise services in clinical oncology settings seems an effective approach for increasing access to exercise-based rehabilitation for individuals on cancer treatment. While this model appears feasible for patients/clinicians, efforts are required to optimize service integration both in the short and long term. Key priorities include seeking [local] actions to address issues relating to funding and organizational buy-in. Important considerations may include developing an implementation plan to guide the implementation process, expanding the patient core management team to include staff from the exercise rehabilitation unit, and exploring the role of patient feedback in increasing clinician participation (e.g., treating oncologists and nurses) in the referral process. Future research should consider effective strategies to promote patients’ sense of self-efficacy and behavioral control and, further, the place of audit and feedback in improving exercise service delivery and overall service implementation.
- ItemOpen AccessA statistical investigation into the validity and reliability of the human figure drawing test(1976) McEwan, Beverley Janet; Shamley, DelvaThe objective of the present study is to statistically investigate the validity and reliability of the Koppitz Human Figure Drawing Test. 300 children aged eight years to eleven years were tested on the 1) Human Figure Drawing Test, 2) Goodenough Draw-a-man Test, 3) Wechsler Intelligence Scale for Children, and 4) New South African Group Test - Junior K, for the intellectual assessment, and on the 1 ) Human Figure Drawing Test, 2) Rutter Parent ( A2) Questionnaire, 3) Rutter Teacher (82) Scale, and 4) the California Test of Personality for the emotional assessment. 224 children aged 6 years to 12 years were assessed for one week test-retest reliability; 175 children aged 8 years to 14 years for one month test-retest reliability; and one hundred drawings were scored for each of inter- and intra-scorer reliability. The results indicate that (1) the Human Figure Drawing Test is not a valid indicator of emotional and behavioural adjustment or as a measure of intelligence, except at the Borderline Range for mental Retardation; and (2) highly significant test-retest and scorer reliabilities were obtained. It is concluded that the Human Figure Drawing Test cannot be regarded as a useful clinical technique.
- ItemOpen AccessSystematic review: Availability, effectiveness and safety of assisted reproductive techniques in Sub-Saharan Africa(2018) Botha, Barend HJ; Dyer, Silke; Shamley, DelvaSTUDY QUESTION: What is the evidence pertaining to availability, effectiveness and safety of assisted reproductive technology (ART) in sub-Saharan Africa? SUMMARY ANSWER: According to overall limited and heterogeneous evidence, availability and utilization of ART are very low, clinical pregnancy rates largely compare to other regions but are accompanied by high multiple pregnancy rates, and in the near absence of data on deliveries and live births the true degree of effectiveness and safety remains to be established. WHAT IS KNOWN ALREADY: In most world regions, availability, utilization and outcomes of ART are monitored and reported by national and regional ART registries. In sub-Saharan Africa there is only one national and no regional registry to date, raising the question what other evidence exists documenting the status of ART in this region. STUDY DESIGN, SIZE, DURATION: A systematic review was conducted searching PUBMED, SCOPUS, AFRICAWIDE, WEB OF SCIENCE and CINAHL databases from January 2000 to June 2017. A total of 29 studies were included in the review. The extracted data were not suitable for meta-analysis. PARTICIPANTS/MATERIALS, SETTING, METHOD: The review was conducted according to PRISMA guidelines. All peer-reviewed manuscripts irrespective of language or study design that presented original data pertaining to availability, effectiveness and safety of ART in sub-Saharan Africa were eligible for inclusion. Selection criteria were specified prior to the search. Two authors independently reviewed studies for possible inclusion and critically appraised selected manuscripts. Data were analyzed descriptively, being unsuitable for statistical analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The search yielded 810 references of which 29 were included based on the predefined selection and eligibility criteria. Extracted data came from 23 single centre observational studies, 2 global ART reports, 2 reviews, 1 national data registry and 1 community-based study. ART services were available in 10 countries and delivered by 80 centres in 6 of these. Data pertaining to number of procedures existed from 3 countries totalling 4619 fresh non-donor aspirations in 2010. The most prominent barrier to access was cost. Clinical pregnancy rates ranged between 21.2% to 43.9% per embryo transfer but information on deliveries and live births were lacking, seriously limiting evaluation of ART effectiveness. When documented, the rate of multiple pregnancy was high with information on outcomes similarly lacking. LIMITATIONS, REASONS FOR CAUTION: The findings in this review are based on limited data from a limited number of countries, and are derived from heterogeneous studies, both in terms of study design and quality, many of which include small sample sizes. Although representing best available evidence, this requires careful interpretation regarding the degree of representativeness of the current status of ART in sub-Saharan Africa. WIDER IMPLICATIONS OF THE FINDINGS: The true extent and outcome of ART in sub-Saharan Africa could not be reliably documented as the relevant information was not available. Current efforts are underway to establish a regional ART data registry in order to report and monitor availability, effectiveness and safety of ART thus contributing to evidence-based practice and possible development strategies. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. The authors had no competing interests. TRIAL REGISTRATION NUMBER: PROSPERO CRD42016032336
- ItemOpen AccessThe feasibility and potential effectiveness of a conventional and exergame intervention to alter balance-related outcomes including fall risk: a mixed methods study(2020) Rogers, Christine; Amosun, Seyi Ladele; Shamley, DelvaIntroduction: Fall risk, occurrence and injury is increasing as the world ages, and Africa and other emerging regions will not be spared. Similarly, the rise of noncommunicable diseases, compressed morbidity and lack of physical activity present major challenges. This novel feasibility study explored the use of an exergaming technology compared with a conventional, evidence-based exercise programme (Otago Exercise Programme) to reduce fall risk by improving balance, and to inform a large-scale randomised control trial. Methodology: Mixed methods study in independent older adults with established fall risk. The quantitative component employed feasibility RCT methodology. Cluster randomisation assigned interventions to sites. Single blinding was used. Both interventions were offered for six months. A variety of balance-related endpoints (e.g., Timed Up and Go, Dynamic Gait Index, Mini-BESTest) were used to find the most applicable. Patient-centred variables included questionnaires regarding depression, physical activity levels, quality of life and estimates of self-efficacy for exercise. Qualitative focus groups explored participants' experiences of falls and the exergaming intervention using a phenomenology lens. Results: Site and participant recruitment was simple and readily achievable, with low numbers need to screen required. Eligibility criteria were confirmed and more added. Adherence and attrition were major challenges. Cluster randomisation appeared to exacerbate between-group differences at baseline. The exergaming intervention produced preliminary evidence in its favour, with results approaching Minimal Clinically Important Difference compared with the evidence-based intervention. The experience of the exergaming intervention was regarded as positive by focus group participants. Barriers and facilitators are reported. Discussion: Methodological issues in the literature have prevented firm consensus on the use of exergaming in falls prevention, although studies are abundant. The current study used rigorous methodology in the novel context of a developing region, which offers numerous challenges for older adults. Implications for a large-scale, fully funded RCT are discussed. Lessons learned can be used to scale up service delivery for an under-served population; and promote the aim of well-being for all at all ages.
- ItemOpen AccessThe relationship between genes associated with the pain pathways and the development of chronic shoulder pain and disability in South African breast cancer survivors(2024) Firfirey, Firzana; Shamley, Delva; September, Alison VBackground A growing challenge in South Africa (SA) healthcare is the frequency of chronic shoulder pain and disability among breast cancer survivors (BCS). Compounding this issue is that a significant number of BCS in South Africa are low-income individuals, exacerbating the economic burden associated with managing chronic pain and disability. These sequelae can last for as much as 6 years post-surgery and thereby negatively impact the overall quality of life. The current standard treatment in SA for acute and chronic pain include opioids and opioid derivatives. Several risk factors have been highlighted to increase susceptibility to developing the sequelae which include severe acute post-operative pain and genetics. Polymorphisms within genes functioning within the opioid signalling and pain pathways have been implicated in variability in opioid use and the development of chronic musculoskeletal pain and disability conditions. The SA population has a diverse genetic background and an increasing BCS cohort that are of mixed ancestry. This thesis therefore sought to identify potential genetic contributors to variability in pain response and to understand the development of chronic pain and disability in SA BCS of mixed ancestry background. The study aimed to (i) assess chronic shoulder pain and disability symptoms using self reported outcome measures in a unique SA BCS cohort; (ii) investigate non-genetic and genetic risk factors associated with chronic pain and disability; (iii) explore the genetic variability in key genes within the opioid signalling and pain pathways and (iv) characterise the potential biological and functional networks related to the opioid signalling and pain pathways. The objectives included : i. Describing the prevalence of chronic pain and disability in BCS using the Shoulder Pain and Disability Index (SPADI) in the SA cohort of mixed ancestry ii. Examine the genetic association between eight prioritised single nucleotide polymorphisms in three candidate genes: (I) ATP-Binding Cassette- Subfamily B, Member 1 Gene (ABCB1); (rs1045642 G>A; rs1128503 G>A), (II) Opioid Receptor, Mu 1 Gene (OPRM1); (rs1799971 A>G; rs540825 T>A) and (III) Catechol-O-Methyl Transferase Gene (COMT); (rs6269 A>G; rs4633 C>T; rs4818 C>G; rs4680 G>A) and the prevalence of chronic pain and disability. iii. Evaluate the gene-gene interaction and association between prioritised SNPs for ABCB1 (rs1045642 G>A; rs1128503 G>A), OPRM1 (rs1799971 A>G; rs540825 T>A) and COMT (rs6269 A>G; rs4633 C>T; rs4818 C>G; rs4680 G>A), and the prevalence of chronic pain and disability in the SA BCS. iv. Conduct bioinformatic analyses to comprehensively examine the functional effects of the prioritised SNPs, identify associated networks and identify potential protein network partners relative to the opioid signalling and pain pathway. Methods A cross-sectional retrospective study was followed (Chapter Error! Reference source not found.), that enrolled two hundred and fifty-two SA BCS. This study was a sub-study of a larger project approved by the Human Research Ethics Committee of the Faculty of Health Sciences within the University of Cape Town (HREC: 312/2012, 125/2017). Qualifying participants were BCS that were diagnosed with unilateral breast cancer ( >1yr before study), older than 18yrs, had no history of neck or shoulder pathology and self-identified as mixed ancestry. Patient-reported pain, disability, and combined symptoms associated with shoulder pathologies were evaluated using the Shoulder Pain and Disability Index (SPADI). Participants scores were calculated and categorized into no-low (A), OPRM1 (rs1799971 A>G), and COMT (rs4680 G>A) . Statistical analysis was performed to describe the relationship between a convenient sample's clinical variables and total drug doses. Moreover, analyses were performed to examine differences in outcome measure scores between the three time points, T1 (pre-operative), T2 ( 3-month post-operative), and T3 (1- year post-operative). Evaluation of the individual genotype, and allele frequencies of each SNPs for each gene between groups were also examined. Haplotype frequencies were statistically inferred for all SNPs within each gene and evaluated between groups. As a proxy for gene-gene interaction, inferred allele–allele combination frequencies were evaluated using the individual genotype data for each SNP. Nonparametric and parametric statistical tests were employed where appropriate, with statistical significance accepted at pA-rs1045642 G>A) haplotype analysis, the inferred G-A (p=0.029, OR: 0.00, 95% CI: 0.00-0.00) haplotype was significantly associated with reduced likelihoods of reporting moderate-high disability. In addition, the inferred A-A (p=0.029, OR:0.63, 95% CI: 0.37-1.06) haplotype was also significantly associated with reduced likelihood of reporting moderate-high combined (pain and disability). The OPRM1 (rs1799971 A>G – rs540825 T>A) inferred G-T (p=0.019, OR:0.33, 95% CI: 0.14-0.75) haplotype was significantly associated with reduced likelihoods of reporting moderate-high pain. Inferred haplotype analysis of five COMT haplotypes noted significant associations for H2-H5, the most notable associations being for the rs6269 A>G -rs4680 G>A genetic interval. This analysis revealed the G-G (p=0.026, OR: 0.67, 95% CI: 0.38-1.18) and A-A (p=0.007, OR: 2.09, 95% CI: 0.89-4.88) haplotypes were associated with reduced and increased likelihood of reporting moderate-high pain, respectively. Gene–gene interaction analyses demonstrated significant associations between the ABCB1 (rs1045642 G>A) – OPRM1 (rs1799971 A>G – rs540825 T>A) and the ABCB1 (rs1045642 G>A) – OPRM1 (rs1799971 A>G). The inferred A-A-T (p=0.029, OR: 0.58, 95% CI: 0.18-1.45) and A-A (p=0.008, OR: 0.44, 95% CI:0.24-0.80) allele-allele combinations were associated with reduced likelihoods of reporting moderated-high combined (pain and disability). ABCB1 (rs1045642 G>A) – OPRM1 (rs540825 T>A) combination analyses demonstrated that the A-T (p=0.019, OR: 0.62, 95% CI: 0.33- 1.16/p=0.014, OR:0.62, 95% CI:0.35-1.10) combination was associated with reduced likelihood of reporting moderate-high disability/combined (pain and disability) symptoms. While the alternate G-A (p=0.021, OR: 1.57, 95% CI: 0.30-3.10/p=0.030, OR: 1.50, 95% CI: 0.78-2.86) combination was associated with increased likelihood of reporting moderate high disability/combined (pain and disability) symptoms. The OPRM1 (rs1799971- rs540825) - COMT (rs4680) combination analyses demonstrated that the A-T-A (p=0.008, OR: 1.36, 95% CI: 0.77-2.41) and G-T-G (p=0.004, OR: 0.00, 95% CI: 0.00-0.00) were associated with increased, and reduced likelihoods of reporting moderate-high pain. Similarly, the OPRM1 (rs1799971 A>G)-COMT (rs4680 G>A) allele-allele combinations A-A (p=0.004, OR: 1.35, 95% CI: 0.85-2.15), and G-G (p=0.010, OR: 0.23, 95% CI: 0.05- 1.03) combinations were associated increased and reduced likelihoods of reporting moderate-high pain and combined (pain and disability). The OPRM1 (rs540825 T>A) - COMT (rs4680 G>A) A-A (p=0.012, OR: 1.89, 95% CI: 0.81-4.38) allele-allele combination was associated increased likelihoods of reporting moderate-high combined (pain and disability). Analyses of the ABCB1 (rs1128503 - rs1045642) - COMT (rs4680) combination demonstrated that the A-A-G (p=0.006, OR:0.68, 95% CI: 0.27-1.71) were significantly associated with reduced likelihood of reporting combined (pain and disability). For the 2-SNP pairing, the ABCB1-COMT (rs4680 G>A) G-A allele combinations were associated with increased likelihoods of reporting moderate-high pain (p=0.005, OR: 2.08, 95% CI: 1.12-3.84), disability (p=0.018, OR: 1.16, 95% CI: 0.62-2.15), and combined (p=0.008, OR: 1.94, 95% CI: 1.02-3.69) groups, pA, and the prevalence of disability, indicating movement-related pain. Despite the absence of an independent association for the functional variant rs1799971 A>G, and rs540825 T>A, for OPRM1, haplotype analyses showed a correlation, supporting the relationship of pain treated with opioids being impacted by this gene. In addition to the independent association observed for COMT rs4680 G>A, gene interactions were observed highlighting the role of collective modulation in pain and disability in the present cohort. Additionally, in-silico analyses revealed strong relationships between the genes and important pathways and mechanisms, further strengthening and supporting the hypotheses presented in the aims of this study. The clinical implications of this study aimed to assist in the understanding of the pain mechanisms and opioid pathways towards the development of novel and innovative therapeutics for pain, in personalized medicine.
- ItemOpen AccessTowards Evidence-Based Implementation of Pharmacogenomics in Southern Africa: Comorbidities and Polypharmacy Profiles across Diseases(Multidisciplinary Digital Publishing Institute, 2023-07-26) Soko, Nyarai Desiree; Muyambo, Sarudzai; Dandara, Michelle T. L.; Kampira, Elizabeth; Blom, Dirk; Jones, Erika S. W.; Rayner, Brian; Shamley, Delva; Sinxadi, Phumla; Dandara, ColletPharmacogenomics may improve patient care by guiding drug selection and dosing; however, this requires prior knowledge of the pharmacogenomics of drugs commonly used in a specific setting. The aim of this study was to identify a preliminary set of pharmacogenetic variants important in Southern Africa. We describe comorbidities in 3997 patients from Malawi, South Africa, and Zimbabwe. These patient cohorts were included in pharmacogenomic studies of anticoagulation, dyslipidemia, hypertension, HIV and breast cancer. The 20 topmost prescribed drugs in this population were identified. Using the literature, a list of pharmacogenes vital in the response to the top 20 drugs was constructed leading to drug–gene pairs potentially informative in translation of pharmacogenomics. The most reported morbidity was hypertension (58.4%), making antihypertensives the most prescribed drugs, particularly amlodipine. Dyslipidemia occurred in 31.5% of the participants, and statins were the most frequently prescribed as cholesterol-lowering drugs. HIV was reported in 20.3% of the study participants, with lamivudine/stavudine/efavirenz being the most prescribed antiretroviral combination. Based on these data, pharmacogenes of immediate interest in Southern African populations include ABCB1, CYP2B6, CYP2C9, CYP2C19, CYP2D6 CYP3A4, CYP3A5, SLC22A1, SLCO1B1 and UGT1A1. Variants in these genes are a good starting point for pharmacogenomic translation programs in Southern Africa.